Drug-resistant tuberculosis management

Drug-resistant tuberculosis (DR-TB) is a form of tuberculosis caused by Mycobacterium tuberculosis strains that are resistant to one or more first-line anti-tuberculosis medicines. Diagnosis is confirmed in the laboratory using World Health Organization (WHO)-recommended rapid genotypic tests such as GeneXpert or conventional phenotypic culture and drug susceptibility testing (DST).

Clinical presentation

The clinical features of drug-resistant tuberculosis are similar to those of drug-susceptible tuberculosis and may include:

Persistent cough
Blood-stained sputum (haemoptysis)
Fever
Night sweats
Weight loss

Drug resistance should be suspected in patients with the following risk factors:

History of previous tuberculosis treatment, including:
- Treatment failure after first-line anti-tuberculosis medicines.
- Relapse or return after loss to follow-up without recent treatment failure.
- Persistent sputum smear positivity at month two or later during first-line tuberculosis treatment.
Close contact with a confirmed drug-resistant tuberculosis case.
Healthcare workers presenting with symptoms of tuberculosis.
Individuals from high-risk congregate settings, including prisoners, urban poor, miners, and people who inject drugs (PWIDs).

All adults and children with presumptive drug-resistant tuberculosis should undergo the Xpert MTB/RIF test as the initial diagnostic test to ensure universal drug susceptibility testing coverage.

Pharmacological treatment

When rifampicin-resistant (RR-TB) or multidrug-resistant tuberculosis (MDR-TB) is diagnosed, communicate promptly with the District TB and Leprosy Coordinator (DTLC) for treatment initiation. Treatment should follow national guidelines and, where indicated, recommendations from the Drug-Resistant TB (DR-TB) Consilium.

Recommended MDR/RR-TB treatment regimens for adults and children over 12 years

Patient condition	Intensive phase	Continuation phase	Alternative medicines if needed*
MDR/RR-TB susceptible to fluoroquinolones	6 months: Lfx + Bdq + Lzd + Cfz + Cs	12 months: Lfx + Cfz + Cs	E, Z, Pto, PAS
MDR/RR-TB with fluoroquinolone resistance (pre-XDR or XDR-TB)	6 months: Bdq + Lzd + Cfz + Cs + Dlm	14 months: Lzd + Cfz + Cs	E, Z, Pto, PAS
Central nervous system tuberculosis	6 months: Lfx + Lzd + Cs + Pto + Z	14 months: Lfx + Lzd + Cs + Z	High-dose isoniazid (INHHD) if low-level isoniazid resistance (inhA mutation)
Pregnant women with RR/MDR-TB	20 months: Lfx + Cs + E + Cfz + Z	Individualized regimen	Consult the DR-TB Consilium. Consider strengthening the regimen postpartum by adding Bdq and Lzd for six months where appropriate.

*Alternative medicines should only be used after consultation with the DR-TB Consilium based on drug susceptibility testing, previous drug exposure, and likelihood of effectiveness.

Recommended treatment regimens for children under 12 years

Children 6–12 years

Patient condition	Intensive phase	Continuation phase	Alternative medicines if needed
RR/MDR-TB susceptible to fluoroquinolones	6 months: Lfx + Bdq + Lzd + Cs	3 months: Lfx + Lzd + Cs	Cfz, Dlm, E (if susceptible), Z
RR/MDR-TB with fluoroquinolone resistance (pre-XDR or XDR-TB)	6 months: Bdq + Lzd + Cs + PAS	3 months: Lzd + Cs + PAS	Cfz, Dlm, E (if susceptible), Z

Children 3–6 years

Patient condition	Treatment regimen	Alternative medicines if needed
RR/MDR-TB susceptible to fluoroquinolones	9 months: Lfx/Mfx + Lzd + Cs + Eto	Cfz, Dlm, PAS, E (if susceptible), Z. Ethionamide (Eto) should not be used if an inhA mutation is present.
RR/MDR-TB with fluoroquinolone resistance	6 months: Lzd + Cs + Dlm + Eto, followed by 3 months: Lzd + Cs + Eto	Cfz, PAS, E (if susceptible), Z. Ethionamide should not be used if an inhA mutation is present.

Children under 3 years

Patient condition	Treatment regimen	Alternative medicines if needed
RR/MDR-TB susceptible to fluoroquinolones	9 months: Lfx/Mfx + Lzd + Cs + Eto	Cfz, PAS, E (if susceptible), Z. Ethionamide should not be used if an inhA mutation is present.
RR/MDR-TB with fluoroquinolone resistance	6 months: Lzd + Cs + PAS + Eto, followed by 3 months: Lzd + Cs + PAS	Cfz, Dlm, E or Z (if susceptible). Cfz is preferred over Eto when a 50 mg capsule is available.

Modified short treatment regimen

Patients aged 15 years and above

Patient condition	Intensive phase	Continuation phase
Eligible for the modified short treatment regimen	6 months: Bdq + Lzd + Lfx + Cfz + Cs + Z	3–5 months: Lfx + Cfz + Cs + Z
Eligible for the modified short treatment regimen but unable to tolerate linezolid (haemoglobin <8 g/dL, neutrophils <0.75 × 10⁹/L, platelets <50 × 10⁹/L, severe peripheral neuropathy grade ≥2, or optic neuritis grade ≥2 at baseline)	6 months: Bdq + Dlm + Lfx + Cfz + Cs + Z	3–5 months: Lfx + Cfz + Cs + Z

Important note

Selection of drug-resistant tuberculosis regimens should always be guided by drug susceptibility testing, previous treatment history, patient age, pregnancy status, disease severity, and recommendations from the District TB and Leprosy Coordinator (DTLC) and the Drug-Resistant TB (DR-TB) Consilium. Regular clinical and laboratory monitoring is essential throughout treatment to assess response, detect adverse drug reactions, and promote treatment adherence.

Imeandikwa:

Ijumaa, 26 Juni 2026, 7:32:30 UTC

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